Tetrahydrophthalazinone inhibitor of phosphodiesterase with in vitro activity against intracellular trypanosomatids

Authors :: Guy Caljon
Louis Maes
Geert Jan Sterk
Maria de Nazaré Correia Soeiro
Raiza Brandão Peres
Titilola D. Kalejaiye
Julianna Siciliano de Araújo
Rob Leurs
Patrícia Bernardino da Silva
Marcos Meuser Batista
Harry P. de Koning
AIMMS
Medicinal chemistry
Source :: De Araújo, J S, Peres, R B, Da Silva, P B, Batista, M M, Sterk, G J, Maes, L, Caljon, G, Leurs, R, De Koning, H P, Kalejaiye, T D & De Nazaré Correia Soeiro, M 2021, ' Tetrahydrophthalazinone inhibitor of phosphodiesterase with in vitro activity against intracellular trypanosomatids ', Antimicrobial agents and chemotherapy, vol. 65, no. 3, e00960-20, pp. 1-5 . https://doi.org/10.1128/AAC.00960-20, Antimicrob Agents Chemother, Antimicrobial agents and chemotherapy, 65(3):e00960-20, 1-5. American Society for Microbiology, Antimicrobial agents and chemotherapy
Publication Year :: 2021
Publisher :: American Society for Microbiology, 2021.
Abstract: The phosphodiesterase inhibitor tetrahydrophthalazinone NPD-008 was explored by phenotypic in vitro screening, target validation, and ultrastructural approaches against Trypanosoma cruzi . NPD-008 displayed activity against different forms and strains of T. cruzi (50% effective concentration [EC 50 ], 6.6 to 39.5 μM). Increased cAMP levels of T. cruzi and its combination with benznidazole gave synergistic interaction.

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